Studies on the ocular pharmacology of prostaglandin D2.
Prostaglandin D2 (PGD2) exerts a variety of biologic actions in the eye; these include ocular hypotension and inflammatory effects on the conjunctiva. The profile of activity of PGD2 in ocular tissues was compared to that of BW 245C, a selective agonist for the PGD2-sensitive (DP) receptor, and to that of the biologically active metabolites of PGD2, 9 alpha,11 beta-prostaglandin F2 (9 alpha,11 beta-PGF2) and prostaglandin J2 (PGJ2). PGD2 produced a dose-dependent decrease in intraocular pressure and in the conjunctiva it caused increased conjunctival microvascular permeability, eosinophil infiltration and goblet cell depletion. Although BW 245C was equipotent to PGD2 as an ocular hypotensive agent, it did not cause pathological effects in the conjunctiva. Thus, the ocular hypotensive effect of PGD2 may be separated from inflammatory effects on the conjunctiva by employing a selective DP-receptor agonist such as BW 245C. 9 alpha,11 beta-PGF2 was a weak ocular hypotensive and did not cause conjunctival inflammation. PGJ2 produced no significant effect on intraocular pressure. PGJ2 did not elicit a microvascular permeability response in the conjunctiva, but was inflammatory in other respects and caused eosinophil infiltration and goblet cell depletion similar to PGD2. Thus, both the ocular hypotensive actions and the conjunctival pathology of PGD2 may be replicated individually by employing PGD2 analogues and metabolites.
Woodward
D F
DF
Allergan, Inc., Department of Pharmacology, Irvine, California 92715.
Hawley
S B
SB
Williams
L S
LS
Ralston
T R
TR
Protzman
C E
CE
Spada
C S
CS
Nieves
A L
AL
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003228:Conjunctiva / Q000098:blood supply / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects; D005070:Evans Blue; D005123:Eye / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006827:Hydantoins / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000031:analogs & derivatives; D011817:Rabbits
D006827:Hydantoins; D005070:Evans Blue; C037112:9-deoxy-delta-9-prostaglandin D2; C030669:BW 245C; D015237:Dinoprost; D015230:Prostaglandin D2